FIG. 1A is a schematic diagram 101 of a nerve (adapted from www.mayoclinic.org/peripheral-nerve-tumors-benign/diagnosis.html). A nerve 11 contains fascicles (bundles) 12 of individual nerve fibers 13 of neurons. FIG. 1B is a schematic diagram 102 of the structure of a spinal nerve 11 that includes its surrounding epineurium 14, which includes connective tissue and blood vessels 15, one or more fascicles (fasciculus) 12, each of which is surrounded by perineurium 17. Within a fascicle 12 is a plurality of axons 13 each having a myelin sheath surrounded by endoneurium tissue 18 (credit to internet sources-data obtained from: en.wikipedia.org/wiki/Nerve_fascicle and trc.ucdavis.edu/mjguinan/apc100/modules/nervous/pns/nerve1/nerve1.html (URL no longer active)).
Typically a nerve action potential (NAP) or compound nerve action potential (CNAP), which is a summated potential of the action potentials in all the axons in a nerve, as a signal travels down a nerve, is sensed using an electrical sensor probe that detects the waveform of a voltage associated with the NAP. Accordingly, traditional methods used electrical stimulation to trigger a NAP signal in a nerve. One disadvantage of using electrical stimulation is that the electrical signal applied to stimulate one nerve fiber will generally stimulate a plurality of surrounding nerve fibers (even nerve fibers in other fascicles than the fascicle containing the nerve of interest) to also trigger NAP signals in those other nerve fibers: Present conventional neuromodulation technology is based on the generation of electric fields around the neuron. The spatial differential voltage along the axons, commonly referred to as the driving function, results in a depolarization of the neural membrane. This depolarization results in action-potential generation, which is then transmitted to target organ where it produces a characteristic effect. The electric field is significantly influenced by the electrical impedance of the tissues.
Extraneural electrodes, such as the Flat Interface Nerve Electrode (FINE), have demonstrated fascicular selectivity (to within about 400 μm). The perineurium, which surrounds a plurality of nerve axons and defines the individual fascicle, typically has a high impedance. This causes the voltage distribution to be fairly uniform within at least a portion of a fascicle (while also being electrically isolated from neighboring fascicles), hence limiting the possibility of sub-fascicular selectivity when using electrical stimulation. While the spatial selectivity of these extraneural electrodes (such as the FINE) has been successfully shown to produce functional neural stimulation in clinical applications, neuromodulation applications such as hand-grasp, sensory-stimulation applications for artificial prostheses, and control of autonomic functions such as cardiac rate via Vagus-nerve stimulation, require, in some cases, selection of at most one fascicle and even greater sub-fascicular spatial selectivity (i.e., selection of a single axon or just a few axons but not all the axons in the single fascicle) than is typically possible using electrical stimulation alone, such that separate signals are delivered to different axons within one fascicle.
As a convention used herein, a nerve will be defined as a collection of individual nerve fibers (i.e., axons) of individual nerve cells (neurons) that together form a set of nerve pathways (an integrated set of pathways for signal propagation within the nervous system). Subsets of the individual nerve fibers are each bundled into one of a plurality of fascicles that together form the nerve. Action potentials can occur in the axon portion of individual nerve cells. A series of individual nerve fibers that together form an integrated signal pathway starting at a sensory-receptor nerve ending and extending to the brain will be referred to as a sensory-nerve pathway, while a series of individual nerve fibers that together form an integrated signal pathway starting at the brain and extending to a muscle cell will be referred to as a motor-nerve pathway. A sensory-nerve pathway that carries auditory signals will be referred to as an auditory-nerve pathway, and a sensory-nerve pathway that carries signals from the sense-of-balance organs (e.g., the vestibular organs of the inner ear, or perhaps the eyes) will be referred to as a sense-of-balance nerve pathway. A sensory-nerve pathway that carries olfactory signals will be referred to as an olfactory-nerve pathway, a sensory-nerve pathway that carries taste signals will be referred to as a taste-nerve pathway, and a sensory-nerve pathway that carries tactician signals will be referred to as a tactile-nerve pathway.
Within each fascicle of a nerve, there will typically be a plurality of sensory-nerve pathways and a plurality of motor-nerve pathways, wherein the number of sensory-nerve pathways will typically be about fifteen times as many as the number of motor-nerve pathways. As well, a series of individual nerve fibers may together form an integrated pathway starting at one of various internal organs and ending in the brain, with then other series of individual nerve fibers together forming an integrated pathway starting at the brain and extending to some internal end organ (such as the digestive tract, the heart, or blood vessels) as part of the autonomic nervous system; and a series of individual nerve fibers may together form an integrated pathway within the brain referred to as a tract. As used herein, a nerve bundle or fascicle refers to a collection of nerve fibers that subserve a common or similar function (e.g., a fascicle may support a plurality of different motor-nerve pathways and thus motor-control signals needed for the muscles for a hand grasp, for example; similarly the same and/or a nearby fascicle may support a plurality of corresponding sensory-nerve pathways and thus sensory signals that provide the brain with feedback for the hand grasp).
U.S. patent application Ser. No. 12/018,185 filed Jan. 22, 2008 by Mark P. Bendett and James S. Webb, titled “Hybrid Optical-Electrical Probes” (now U.S. Pat. No. 7,883,536 issued Feb. 8, 2011), which is incorporated herein by reference in its entirety, describes an optical-signal vestibular-nerve stimulation device and method that provides different nerve stimulation signals to a plurality of different vestibular nerves, including at least some of the three semicircular canal nerves and the two otolith organ nerves. In some embodiments described in that patent application, balance conditions of the person are sensed by the implanted device, and based on the sensed balance conditions, varying infrared (IR) nerve-stimulation signals are sent to a plurality of the different vestibular nerves. Also described is a method that includes obtaining light from an optical source; transmitting the light through an optical fiber between a tissue of an animal and an optical transducer, and detecting electrical signals using conductors attached to the optical fiber. The application also describes an apparatus that includes an optical source, an optical transmission medium operatively coupled to the optical source and configured to transmit light from the optical source to respective nerves of each of one or more organs of an animal, an electrical amplifier, and an electrical transmission medium integral with the optical transmission medium and operatively coupled to the electrical amplifier, wherein the electrical transmission medium is configured to transmit an electrical signal from the respective nerves to the electrical amplifier.
U.S. Pat. No. 6,921,413 issued Jul. 26, 2005 to Mahadevan-Jansen et al., titled “Methods and devices for optical stimulation of neural tissues,” and U.S. patent application Ser. No. 11/257,793 filed Oct. 24, 2005 by Webb et al. (now U.S. Pat. No. 7,736,382, which issued Jun. 15, 2010), titled “Apparatus for Optical Stimulation of Nerves and Other Animal Tissue,” are each incorporated herein by reference in their entirety. Both of these describe optical stimulation of nerves in general.
U.S. Patent Application Publication No. US 2006/0161227, of Walsh et al., titled “Apparatus and Methods for Optical Stimulation of the Auditory Nerve,” is incorporated herein by reference in its entirety. This application describes a cochlear implant placed in a cochlea of a living subject for stimulating the auditory system of the living subject, where the auditory system comprises auditory neurons. In one embodiment, the cochlear implant includes a plurality of light sources {Li}, placeable distal to the cochlea, each light source being operable independently and adapted for generating an optical energy, Ei, wherein i=1, . . . , N, and N is the number of the light sources, and delivering means placeable in the cochlea and optically coupled to the plurality of light sources, {Li}, such that in operation, the optical energies {Ei} generated by the plurality of light sources {Li} are delivered to target sites, {Gi}, of auditory neurons, respectively, wherein the target sites G1 and GN of auditory neurons are substantially proximate to the apical end and the basal end of the cochlea, respectively.
U.S. Patent Application Publication No. US 2005/0004627 titled “Auditory midbrain implant” filed by Peter Gibson et al. on Aug. 26, 2004, is incorporated herein by reference (this application issued as U.S. Pat. No. 7,797,029 on Sep. 14, 2010). This application describes an electrode array that is implantable within the inferior colliculus of the midbrain and/or other appropriate regions of the brain of an implantee and adapted to provide electrical stimulation thereto. The electrode array includes an elongate member having a plurality of electrodes mounted thereon in a longitudinal array. A delivery cannula for delivering the electrode array comprised of two half-pipes is also described.
U.S. Patent Application No. US 2007/0261127 A1 filed Jul. 24, 2006, by Edward S. Boyden and Karl Deisseroth, titled “Light-Activated Cation Channel and Uses Thereof”; U.S. Patent Application No. US 2007/0054319 A1 filed Jul. 24, 2006, by Edward S. Boyden and Karl Deisseroth, titled “Light-Activated Cation Channel and Uses Thereof”; and U.S. Patent Application No. US 2007/0053996 A1 (now abandoned) filed Jul. 24, 2006, by Edward S. Boyden and Karl Deisseroth, titled “Light-Activated Cation Channel and Uses Thereof” are all incorporated herein by reference. These describe compositions and methods for light-activated cation channel proteins and their uses within cell membranes and subcellular regions. They describe proteins, nucleic acids, vectors and methods for genetically targeted expression of light-activated cation channels to specific cells or defined cell populations. In particular the descriptions describe millisecond-timescale temporal control of cation channels using moderate light intensities in cells, cell lines, transgenic animals, and humans. The descriptions provide for optically generating electrical spikes in nerve cells and other excitable cells useful for driving neuronal networks, drug screening, and therapy.
An article authored by Han, Xue, et al. titled “Multiple-Color Optical Activation, Silencing, and Desynchronization of Neural Activity, with Single-Spike Temporal Resolution” (PLoS ONE 2(3): e299. doi:10.1371/journal.pone.0000299, March 2007) is incorporated herein by reference. This article describes targeting the codon-optimized form of the light-driven chloride pump halorhodopsin from the archaebacterium Natronomas pharaonis (hereafter abbreviated Halo) to genetically-specified neurons enables them to be silenced reliably, and reversibly, by millisecond-timescale pulses of yellow light. The article describes that trains of yellow and blue light pulses can drive high-fidelity sequences of hyperpolarizations and depolarizations in neurons simultaneously expressing yellow light-driven Halo and blue light-driven ChR2, allowing for the first time manipulations of neural synchrony without perturbation of other parameters such as spiking rates. The article further describes the Halo/ChR2 system thus constitutes a powerful toolbox for multichannel photoinhibition and photostimulation of virally or transgenically targeted neural circuits without need for exogenous chemicals, thus enabling systematic analysis and engineering of the brain, and quantitative bioengineering of excitable cells.
An article authored by Bernstein, Jacob G., et al. titled “Prosthetic systems for therapeutic optical activation and silencing of genetically-targeted neurons” (Proc Soc Photo Opt Instrum Eng.; 6854: 68540H., May 5, 2008) is incorporated herein by reference. This article describes that the naturally-occurring light-activated proteins channelrhodopsin-2 (ChR2) and halorhodopsin (Halo/NpHR) can, when genetically expressed in neurons, enable them to be safely, precisely, and reversibly activated and silenced by pulses of blue and yellow light, respectively. The article describes the ability to make specific neurons in the brain light-sensitive, using a viral approach. The article also describes the design and construction of a scalable, fully implantable optical prosthetic capable of delivering light of appropriate intensity and wavelength to targeted neurons at arbitrary 3-D locations within the brain, enabling activation and silencing of specific neuron types at multiple locations. The article further describes control of neural activity in the cortex of the non-human primate, a key step in the translation of such technology for human clinical use. The article asserts systems for optical targeting of specific neural circuit elements may enable a new generation of high-precision therapies for brain disorders.
U.S. Patent Application No. US 2009/0210039 A1 filed Jan. 16, 2009, by Edward S. Boyden et al., titled “Prosthetic Systems for Therapeutic Optical Activation and Silencing of Genetically-Targeted Neurons,” is incorporated herein by reference. The application describes an optical prosthesis that permits control of neural circuits that comprises a probe having a set of light sources, drive circuit connections connected to each light source, a housing surrounding the light sources and drive circuit connections, and drive circuitry for driving and controlling the probe. The application also describes drive circuit connections and drive circuitry may optionally provide for wireless communication. The application describes light sources may be light-emitting diodes, lasers, or other suitable sources. The application describes the device may optionally include sensors for monitoring the target cells. The application also describes a multi-dimensional array of probes, each probe having a set of light sources, drive circuit connections connected to each light source, a housing surrounding the light sources and the drive circuit connections, drive circuitry for driving and controlling the probes, and supporting hardware that holds the probes in position with respect to each other and the target cells.
There are patients suffering from incomplete spinal cord injuries that do not result in complete loss of movement and sensation below the injury site. Injuries resulting from an anterior spinal cord injury that include damage to the front of the spinal cord affect pain, temperature, and touch sensation, but leave some pressure and joint sensation, and wherein often motor function is unaffected.
Injuries to the central portion of the spinal cord can result in Central Cord Syndrome and form an incomplete spinal cord injury in which some of the signals from the brain to the body are not received, characterized by impairment in the arms and hands and, to a lesser extent, in the legs. In some injuries, sensory loss below the site of the spinal injury and loss of bladder control may occur. Central Cord Syndrome, which is usually the result of trauma, is associated with damage to the large nerve fibers that carry information directly from the cerebral cortex of the brain to the spinal cord and these large nerves are particularly important for hand and arm function. Symptoms of large nerve fiber damage may include paralysis and/or loss of fine control of movements in the arms and hands, with relatively less impairment of leg movements. Often, the brain's ability to send and receive signals to and from parts of the body below the site of trauma is affected but not entirely blocked.
Spinal injuries caused by a lesion affecting the lateral half of the spinal cord is known as Brown-Séquard syndrome, and is characterized by contralateral hemisensory anesthesia to pain and temperature, ipsilateral loss of propioception, and ipsilateral motor paralysis below the level of the lesion. Tactile sensation is generally spared.
The most common type of spinal cord injury is a spinal contusion wherein the spinal cord is bruised but not severed. The spinal contusion results in inflammation and bleeding in the spinal column near the site of the injury which can kill spinal cord neurons. Finally, injuries to individual nerve cells manifest as a loss of sensory and motor functions in the area of the body to which the injured nerve root corresponds.
Besides such spinal-cord injuries, there are numerous other nerve injuries and pathologies that need treatment. Thus, there is a need to provide therapy (e.g., through stimulation of physiological signals in the patient such as nerve action potentials (NAPs)) that restores such sensations (signals towards the brain) to persons having such injuries, as well as nerve stimulation and/or inhibition for treatment of pain, obesity, epilepsy, depression, and the like. There is also a need to provide therapy that restores motor-nerve (muscle-control) signals from the brain towards muscles or prostheses (through NAP stimulation, inhibition, or both), for motor control as well as treatment of incontinence, irregular heart rhythms, tremors or twitches, and the like.
There is also a need for efficacious apparatus and methods for optically stimulating, and/or optically and electrically stimulating, nerves of the central nervous system (CNS) and/or the peripheral nervous system (PNS) in a living animal in order to generate a nerve action potential (NAP) in one neuron (nerve cell), or in multiple neurons within a nerve bundle or nerve (where the combined individual NAPs form a compound nerve action potential, or CNAP), or similar physiological response in the animal. Optical and/or electrical-and-optical stimulation of neurons can provide more precision in terms of stimulating a particular nerve pathway than is possible using only electrical stimulation.